PROCESS FOR THE PREPARATION OF 8-{4'-[4''-(PYRIMIDIN-2'''-YL)- -PIPERAZIN-1''-YL]-BUTYL}-8-AZA-SPIRO[4,5]DECANE-7,9-DIONE AND OF ITS HYDROCHLORIDES OF HIGH PURITY

Je opísaný spôsob prípravy 8-{4'-[4''-(pyrimidin-2'''-yl)- -piperazin-1''-yl)-butyl}-8-aza-spiro[4,5]dekan-7,9-diónu vzorca (I) a jeho hydrochloridov s vysokou čistotou katalytickou hydrogenáciou 8-{4'-[4''(pyrimidin-2'''-yl)-piperazin-1''-yl)- -but-2'-inyl}-8-aza-spiro[4,5]dekan-7,9-diónu vzorca (II) v prítomnosti paládiového alebo Raney-niklového katalyzátora v inertnom organickom rozpúšťadle a prípadne jeho prevedenie na hydrochlorid, pri ktorom sa kontinuálne pridáva roztok zlúčeniny vzorca (II) v inertnom organickom rozpúšťadle s koncentráciou aspoň 40 % hmotn. do suspenzie katalyzátora v inertnom organickom rozpúšťadle, odstraňuje sa katalyzátor a potom sa izoluje zlúčenina vzorca (I) ako báza a/alebo sa pôsobí na bázu vzorca (I) chlorovodíkom v etanole alebo izopropanole za miešania pri teplote medzi 15 °C a 40 °C a izoluje sa hydrochlorid 8-{4'-[4''-(pyrimidin-2'''-yl)-piperazin-1''-yl]-butyl}- -8-aza-spiro[4,5]dekan-7,9-diónu s teplotou topenia od 188 do 191 °C, alebo sa pôsobí na bázu vzorca (I) chlorovodíkom v etylacetáte alebo izopropanole pri teplote nepresahujúcej 70 °C za miešania a izoluje sa hydrochlorid 8-{4'-[4''-(pyrimidin- -2'''-yl)-piperazin-1''-yl]-butyl}-8-aza-spiro[4,5]dekan- -7,9-diónu s teplotou topenia od 201 do 203 °C.ŕ The invention relates to a process for the preparation of 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione {buspirone} of the formula and of its hydrochlorides by hydrogenating 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]but-2'-ynyl}-8-azaspiro [4.5 ]decane-7,9-dione of the formula in the presence of a palladium or Raney nickel catalyst in an organic solvent and optionally converting the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione into a hydrochloride, in which a solution of 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]but-2'-ynyl}-8-azaspiro [4.5 ]decane-7,9-dione of the formula II in an organic solvent whose concentration is at least 40% by weight is added to a suspension of the catalyst in an organic solvent, the catalyst is removed and a) the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione base of the formula I is isolated and/or b) the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione base of the formula I is treated with hydrogen chloride at 15 to 40 DEG C in ethanol or isopropanol and the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-